Abstract
AIM To assess Dietary myo-inositol in reducing stem cell activation in colitis, and validate p?-cateninS552 as a biomarker of recurrent dysplasia. METHODS We examined the effects of Dietary myo-inositol treatment on inflammation, p?-cateninS552 and pAkt levels by histology and western blot in IL-10-/- and dextran soDium sulfate-treated colitic mice. AdDitionally, we assessed nuclear p?-cateninS552 in patients treated with myo-inositol in a clinical trial, and in patients with and without a history of colitis-induced dysplasia. RESULTS In mice, p?-cateninS552 staining faithfully reported the effects of myo-inositol in reducing inflammation and intestinal stem cell activation. In a pilot clinical trial of myo-inositol administration in patients with a history of low grade dysplasia (LGD), two patients had reduced numbers of intestinal stem cell activation compared to the placebo control patient. In humans, p?-cateninS552 staining Discriminated ulcerative colitis patients with a history of LGD from those with benign Disease. CONCLUSION Enumerating crypts with increased numbers of p?- cateninS552 - positive cells can be utilized as a biomarker in colitis-associated cancer chemoprevention trials.
Original language | English (US) |
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Pages (from-to) | 5115-5126 |
Number of pages | 12 |
Journal | World Journal of Gastroenterology |
Volume | 23 |
Issue number | 28 |
DOIs | |
State | Published - Jul 28 2017 |
Funding
Supported by Veterans Affairs Merit Award, No. IO1CX001353 (to Barrett TA); National Institutes of Health, No. 2R01DK095662-06A1 (to Barrett TA); the National Cancer Institute at the National Institutes of Health, No. N01-CN-35157 (to Bergan R); the Training Program in Oncogenesis and Developmental Biology through the National Cancer Institute, No. NCI T32 CA080621 (to Bradford EM); an Institutional Development Award from the National Institute of General MeDical Sciences of the National Institutes of Health, No. 8 P20GM103527-05; and American Physiological Society STEP-UP Fellowship (to Thompson CA).
Keywords
- Biomarker
- Chemoprevention
- Colitis-associated cancer
- Dysplasia
- Stem cell
ASJC Scopus subject areas
- Gastroenterology